550 research outputs found
Reading in two writing systems: Accommodation and assimilation of the brain's reading network
Bilingual reading can require more than knowing two languages. Learners must acquire also the writing conventions of their second language, which can differ in its deep mapping principles (writing system) and its visual configurations (script). We review ERP (event-related potential) and fMRI studies of both Chinese-English bilingualism and Chinese second language learning that bear on the system accommodation hypothesis: the neural networks acquired for one system must be modified to accommodate the demands of a new system. ERP bilingual studies demonstrate temporal indicators of the brain's experience with L1 and L2 and with the frequency of encounters of words in L2. ERP learning studies show that early visual processing differences between L1 and L2 diminish during a second term of study. fMRI studies of learning converge in finding that learners recruit bilateral occipital-temporal and also middle frontal areas when reading Chinese, similar to the pattern of native speakers and different from alphabetic reading. The evidence suggests an asymmetry: alphabetic readers have a neural network that accommodates the demands of Chinese by recruiting neural structures less needed for alphabetic reading. Chinese readers have a neural network that partly assimilates English into the Chinese system, especially in the visual stages of word identification. © Cambridge University Press 2007.published_or_final_versio
RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord
ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients
Understanding the impact of antibiotic therapies on the respiratory tract resistome: A novel pooled-template metagenomic sequencing strategy
Determining the effects of antimicrobial therapies on airway microbiology at a population-level is essential. Such analysis allows, for example, surveillance of antibiotic-induced changes in pathogen prevalence, the emergence and spread of antibiotic resistance, and the transmission of multi-resistant organisms. However, current analytical strategies for understanding these processes are limited. Culture- and PCR-based assays for specific microbes require the a priori selection of targets, while antibiotic sensitivity testing typically provides no insight into either the molecular basis of resistance, or the carriage of resistance determinants by the wider commensal microbiota. Shotgun metagenomic sequencing provides an alternative approach that allows the microbial composition of clinical samples to be described in detail, including the prevalence of resistance genes and virulence traits. While highly informative, the application of metagenomics to large patient cohorts can be prohibitively expensive. Using sputum samples from a randomised placebo-controlled trial of erythromycin in adults with bronchiectasis, we describe a novel, cost-effective strategy for screening patient cohorts for changes in resistance gene prevalence. By combining metagenomic screening of pooled DNA extracts with validatory quantitative PCR-based analysis of candidate markers in individual samples, we identify population-level changes in the relative abundance of specific macrolide resistance genes. This approach has the potential to provide an important adjunct to current analytical strategies, particularly within the context of antimicrobial clinical trials
Investigating Unique Environmental Contributions to the Neural Representation of Written Words: A Monozygotic Twin Study
The visual word form area (VWFA) is a region of left inferior occipitotemporal cortex that is critically involved in visual word recognition. Previous studies have investigated whether and how experience shapes the functional characteristics of VWFA by comparing neural response magnitude in response to words and nonwords. Conflicting results have been obtained, however, perhaps because response magnitude can be influenced by other factors such as attention. In this study, we measured neural activity in monozygotic twins, using functional magnetic resonance imaging. This allowed us to quantify differences in unique environmental contributions to neural activation evoked by words, pseudowords, consonant strings, and false fonts in the VWFA and striate cortex. The results demonstrate significantly greater effects of unique environment in the word and pseudoword conditions compared to the consonant string and false font conditions both in VWFA and in left striate cortex. These findings provide direct evidence for environmental contributions to the neural architecture for reading, and suggest that learning phonology and/or orthographic patterns plays the biggest role in shaping that architecture
Nuclear receptor NR2F6 inhibition potentiates responses to PD-L1/PD-1 cancer immune checkpoint blockade
Immune checkpoints blockade (ICB) is a viable anti-cancer strategy. Here the authors show that nuclear receptor NR2F6 acts as an immune checkpoint in T cells and, using mouse models and human T cells, they show NR2F6 inhibition might improve current ICB therapy or work as an alternative therapeutic strategy
Home on the Range: Factors Explaining Partial Migration of African Buffalo in a Tropical Environment
Partial migration (when only some individuals in a population undertake seasonal migrations) is common in many species and geographical contexts. Despite the development of modern statistical methods for analyzing partial migration, there have been no studies on what influences partial migration in tropical environments. We present research on factors affecting partial migration in African buffalo (Syncerus caffer) in northeastern Namibia. Our dataset is derived from 32 satellite tracking collars, spans 4 years and contains over 35,000 locations. We used remotely sensed data to quantify various factors that buffalo experience in the dry season when making decisions on whether and how far to migrate, including potential man-made and natural barriers, as well as spatial and temporal heterogeneity in environmental conditions. Using an information-theoretic, non-linear regression approach, our analyses showed that buffalo in this area can be divided into 4 migratory classes: migrants, non-migrants, dispersers, and a new class that we call “expanders”. Multimodel inference from least-squares regressions of wet season movements showed that environmental conditions (rainfall, fires, woodland cover, vegetation biomass), distance to the nearest barrier (river, fence, cultivated area) and social factors (age, size of herd at capture) were all important in explaining variation in migratory behaviour. The relative contributions of these variables to partial migration have not previously been assessed for ungulates in the tropics. Understanding the factors driving migratory decisions of wildlife will lead to better-informed conservation and land-use decisions in this area
Reduction in radiation (fluoroscopy) while maintaining safe placement of pedicle screws during lumbar spine fusion
Draft genome sequence of Wickerhamomyces anomalus LBCM1105, isolated from cachaça fermentation
Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.The authors gratefully acknowledge Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE) and the Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) for support with the sequencing of LBCM1105. This work was supported by CAPES/Brazil (PNPD 2755/2011; PCF-PVE 021/2012), by CNPq (Brazil), processes 304815/2012 (research grant) and 305135/2015-5, and by AUXPE-PVES 1801/2012 (Process 23038.015294/2016-18) from Brazilian Government and by UFOP. C.L. is supported by the strategic program UID/BIA/04050/2013 [POCI-01-0145-FEDER-007569] funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional de Competitividade e Internacionalizacao (POCI). DMRP is a fellow from the CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) - Brazil (310080/2018-5)
Bacteria are important dimethylsulfoniopropionate producers in coastal sediments
Dimethylsulfoniopropionate (DMSP) and its catabolite dimethyl sulfide (DMS) are key marine nutrients, with roles in global sulfur cycling, atmospheric chemistry, signalling and, potentially, climate regulation. DMSP production was previously thought to be an oxic and photic process, mainly confined to the surface oceans. However, here we show that DMSP concentrations and DMSP/DMS synthesis rates were higher in surface marine sediment from e.g., saltmarsh ponds, estuaries and the deep ocean than in the overlying seawater. A quarter of bacterial strains isolated from saltmarsh sediment produced DMSP (up to 73 mM), and previously unknown DMSP-producers were identified. Most DMSP-producing isolates contained dsyB, but some alphaproteobacteria, gammaproteobacteria and actinobacteria utilised a methionine methylation pathway independent of DsyB, previously only associated with higher plants. These bacteria contained a methionine methyltransferase ‘mmtN’ gene - a marker for bacterial DMSP synthesis via this pathway. DMSP-producing bacteria and their dsyB and/or mmtN transcripts were present in all tested seawater samples and Tara Oceans bacterioplankton datasets, but were far more abundant in marine surface sediment. Approximately 108 bacteria per gram of surface marine sediment are predicted to produce DMSP, and their contribution to this process should be included in future models of global DMSP production. We propose that coastal and marine sediments, which cover a large part of the Earth’s surface, are environments with high DMSP and DMS productivity, and that bacteria are important producers within them
A distinct bacterial dysbiosis associated skin inflammation in ovine footrot
Ovine footrot is a highly prevalent bacterial disease caused by Dichelobacter nodosus and characterised by the separation of the hoof horn from the underlying skin. The role of innate immune molecules and other bacterial communities in the development of footrot lesions remains unclear. This study shows a significant association between the high expression of IL1β and high D. nodosus load in footrot samples. Investigation of the microbial population identified distinct bacterial populations in the different disease stages and also depending on the level of inflammation. Treponema (34%), Mycoplasma (29%) and Porphyromonas (15%) were the most abundant genera associated with high levels of inflammation in footrot. In contrast, Acinetobacter (25%), Corynebacteria (17%) and Flavobacterium (17%) were the most abundant genera associated with high levels of inflammation in healthy feet. This demonstrates for the first time there is a distinct microbial community associated with footrot and high cytokine expression
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